THE ROLE OF NOS3 AND CYBA GENE POLYMORPHISM IN THE FORMATION OF COMPLICATIONS OF CHRONIC VIRAL HEPATITIS B
https://doi.org/10.25587/SVFU.2022.27.2.008
Abstract
In the Republic of Sakha (Yakutia), persistently high incidence rates of CVH remain, as well as mortality rates from complications of liver cirrhosis (LC), as the most common complication. It seems relevant to search for genetic predictors of early development of severe complications in CVH patients in the Yakut population. They can be polymorphic variants of the genes for endothelial dysfunction and oxidative stress NOS3 and CYBA. The collection of representative material was carried out on the basis of the Infectious Diseases Department of the State Budgetary Institution of the Republic of Sakha (Yakutia) of the Yakut Republican Clinical Hospital. In total, 47 DNA samples of patients with chronic viral hepatitis В and liver cirrhosis in its outcome, hospitalized in the Infectious Diseases Department from September 2020 to June 2021, were studied. The control group consisted of patients not infected with viral hepatitis, as well as without pathology of the hemostasis system. The experimental part of the study was carried out by real-time PCR with the melting of hybridization products with a fluorescent label, followed by analysis of the RealBest-Genetics melting curves. As a result of the PCR- RFLP analysis of the rs1799983 polymorphism of the NOS3 gene among patients with chronic viral hepatitis, the T allele frequency was 0.09, and the G allele frequency was 0.91. The frequency of the C allele of the rs2070744 polymorphism of the NOS3 gene was 0.05, the frequency of the T allele was 0.95. The frequency of occurrence of the major allele C of the rs4673 polymorphism of the CYBA gene was 0.78, the minor allele T was 0.22. The relationship between the carriage of polymorphisms of these genes and the disease was not found. However, it was found that carriers of the mutant allele for the rs1799983 polymorphism of the NOS3 gene were 1.81 times more likely to develop liver cirrhosis (95 % CI, odds in the groups 0.176–0.098), carriers of the mutant allele for the rs4673 polymorphism of the CYBA gene were more likely to develop cirrhosis liver cirrhosis is 1.9 times higher (95 % CI, odds in groups 0.211–0.111), in carriers of the mutant allele for the rs2070744 polymorphism of the NOS3 gene, the probability of developing liver cirrhosis is 2.03 times higher (95 % CI, odds in groups 0.181–0.089 ). In carriers of the mutant allele for the rs4673 polymorphism of the CYBA gene, shortening of PT and APTT (17.79±10.26 and 35.13±7.82 sec) is observed, which may indicate a greater tendency of this group to hypercoagulability. In carriers of the mutant allele for the rs2070744 polymorphism of the NOS3 gene, shortening of PT and APTT (11.56±0.99 and 30.12±4.45 sec) is observed, which may also indicate a greater tendency of this group to hypercoagulability.
Keywords
About the Authors
Yu. A. SolovievaRussian Federation
Yuliya Alekseevna Solovieva, Senior Lecturer
Institute of Medicine
Department of Hospital Therapy, Occupational Diseases and Clinical Pharmacology
Yakutsk
N. V. Borisova
Russian Federation
Natalia Vladimirovna Borisova, Doctor of Medical Sciences, Professor, Head Department
Institute of Medicine
Department of Normal and Pathological Pharmacology
Yakutsk
References
1. Abdurahmanov D. T., Rozina T. P., Nikulkina E. N. i dr. Protivovirusnaya terapiya hronicheskogo gepatita S: 30-letnyaya istoriya uspekha // Terapevticheskij arhiv. – 2019. – № 11. – S. 110 – 116.
2. Kasimova N. B., Galimzyanov H. M., Sherysheva Yu. V. Trudnosti i uspekhi protivovirusnoj terapii hronicheskogo virusnogo gepatita s // Astrahanskij medicinskij zhurnal. – 2019. – № 2. – S. 6-15.
3. Konopleva M. V., Borisova V. N., Semenenko T. A. i dr. Problemy sovremennoj strategii vakcinacii protiv gepatita V // Epidemiologiya i vakcinoprofilaktika. – 2017. – № 4 (95). – S. 58-64.
4. Gosudarstvennyj doklad “O sostoyanii sanitarno-epidemiologicheskogo blagopoluchiya naseleniya v Respublike Saha (Yakutiya) v 2020 godu”
5. Sistema monitoringa bol’nyh virusnymi gepatitami «Registr bol’nyh virusnymi gepatitami» https://hepreg.ru/login.html
6. Slepcova S. S., Semenov S. I., Borisova N. V. i dr. Osnovnye faktory riska progressirovaniya hronicheskih virusnyh gepatitov v YAkutii // Vestnik Severo-Vostochnogo federal’nogo universiteta. Seriya: Medicinskie nauki. – 2017. – № 4 (9). – S. 89-95.
7. Sofronova A. R., Slepcova S. S., Semenova V. K. i dr. Prichiny progressirovaniya hronicheskih virusnyh gepatitov v Yakutii // Vestnik Severo-Vostochnogo federal’nogo universiteta. Seriya: Medicinskie nauki. – 2016. – № 3 (4). – S. 92-95.
8. Semenov S. I., Fedorov A. I., Osakovskij V. L. i dr. Chastota vstrechaemosti polimorfnyh variantov gena IL28B i genotipov virusa gepatita s u naseleniya YAkutii: klinicheskie iskhody // Zhurnal mikrobiologii, epidemiologii i immunobiologii. – 2017. – № 2. – S. 86-92.
9. Yushchuk N. D., Slepcova S. S., Malov S. I. i dr. Ocenka vneshnih faktorov riska razvitiya gepatocellyulyarnogo raka i markerov geneticheskoj predraspolozhennosti k ego razvitiyu v etnicheskoj gruppe yakutov – muzhchin // Terapevticheskij arhiv. – 2020. – № 1. – S. 56-61.
10. Li H [et al.] Regulation of endothelial-type NO synthase expression in pathophysiology and in response to drugs. Nitric Oxide. 2002; (7):149–164
11. Jin L [et al.] Role and regulation of autophagy and apoptosis by nitric oxide in hepatic stellate cells during acute liver failure. Liver International: Official Journal of the International Association for the Study of the Liver. 2017; 37 (11): 1651–1659. DOI: 10.1111/liv.13476
12. Dhar D., Baglieri J., Kisseleva T., Brenner D. A. Mechanisms of liver fibrosis and its role in liver cancer. Exp Biol Med (Maywood). 2020 Jan; 245 (2): 96-108. doi: 10.1177/1535370219898141. Epub 2020 Jan 10. PMID: 31924111; PMCID: PMC7016420.
13. Ramos-Tovar E., Muriel P. Molecular Mechanisms That Link Oxidative Stress, Inflammation, and Fibrosis in the Liver. Antioxidants (Basel). 2020 Dec 15; 9 (12):1279. doi: 10.3390/antiox9121279. PMID: 33333846; PMCID: PMC7765317.
14. Taratina O. V., Samohodskaya L. M., Krasnova T. N., Muhin N. A. Prognozirovanie skorosti razvitiya fibroza pecheni u bol’nyh hronicheskim gepatitom S na osnove kombinacii geneticheskih i sredovyh faktorov. Al’manah klinicheskoj mediciny. 2017; 45 (5): 392-407. https://doi.org/10.18786/2072-0505-2017-45-5-392-407
15. Taratina O. V., Krasnova T. N., Samohodskaya L. M., Lopatkina T. N., Tkachuk V. A., Muhin N. A. Polimorfizm genov disfunkcii endoteliya i skorost’ progressirovaniya fibroza pecheni pri hronicheskom gepatite S. Terapevticheskij arhiv (arhiv do 2018 g.). 2014; 86 (4):45-51.
Review
For citations:
Solovieva Yu.A., Borisova N.V. THE ROLE OF NOS3 AND CYBA GENE POLYMORPHISM IN THE FORMATION OF COMPLICATIONS OF CHRONIC VIRAL HEPATITIS B. Vestnik of North-Eastern Federal University. Medical Sciences. 2022;(2):72-78. (In Russ.) https://doi.org/10.25587/SVFU.2022.27.2.008